tbuckley/cabot-search huggingface dataset:
A randomized, multi-center phase III trial of adjuvant chemotherapy with gemcitabine and capecitabine (GemCap) compared to capecitabine (Cap) alone in curatively resected biliary tract cancer (BilGemCap Study): KCSG HB20-14.
Authors: Joon Oh Park, Joon Seong Park, Choong-kun Lee, Hong Jae Chon, Sae Byeol Choi, Dae Wook Hwang, Do-Youn Oh, Myung Ah Lee, Jin-Young Jang, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2023)

TPS633 Background: Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage; thus, only 20% of the patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. Recent phase 3 trials using single agent such as Cap or S1 support the role of adjuvant chemotherapy as standard of care in patients with resected BTCs, but the efficacy still needs to be further improved. Therefore, we designed a randomized, multi-center, phase 3 trial comparing GemCap with Cap in curatively resected BTC patients. Methods: The primary endpoint is 24-month disease-free survival (DFS) and secondary endpoints are overall survival (OS), quality of life (QOL), toxicities and exploratory biomarker analysis. Referring to the recent results of BILCAP study, the sample size calculation is based on the assumption that the 24-month DFS would be 50% in the Cap arm, and that treatment with GemCap would improve the 24-months DFS by 10%, from 50% to 60%. As such, 490 patients and 337 events are needed to detect a HR of 0.737, with a two-sided significance level of 5% and 80% power. Patients aged 19 years or older with macroscopically resected intra- or extrahepatic cholangiocarcinoma and muscle-invasive gallbladder cancer (T2-4 or N1-2, M0) are eligible. The Eastern Cooperative Oncology Group (ECOG) performance status have to be 0-1, and adequate renal, hematological, and liver function is required. Patients who had not completely recovered within 12 weeks from surgery or who had previous history of chemotherapy or radiotherapy for BTC are also excluded. Patients are randomly assigned 1:1 to the GemCap arm or the Cap arm, stratified by LN status (N0 vs. N+), resection status (R0 vs. R1) and primary site. After randomization, either oral Cap (1250 mg/m²) twice a day on days 1 to 14 of a 3-weekly cycle (8 cycles), or oral Cap (830 mg/m²) twice a day on days 1 to 21 plus Gem (830 mg/m²) on days 1, 8 and 15 of a 4-weeky cycle (6 cycles) are given. As of September 2022, 147 patents have been randomized to each arm, and updated study status will be presented. This is a collaborative study with Korean Cancer Study Group (KCSG) and Korean Pancreas Surgery Club (KPSC), supported by a grant from the National R&amp;D Program for Cancer Control through the National Cancer Center (NCC) funded by the Ministry of Health &amp; Welfare, Republic of Korea (HA22C0053). This is prospectively registered on ClinicalTrials.gov, NCT0005056. Clinical trial information: NCT0005056 .
The usefulness of indocyanine green (ICG)–guided lymphadenectomy in robotic gastrectomy for advanced gastric cancer: A single-center retrospective study.
Authors: Chul Hyo Jeon, Ho Seok Seo
Journal: Journal of Clinical Oncology (2023)

390 Background: In performing radical gastrectomy for advanced gastric cancer, the method to evaluate the achievement of lymphadenectomy is under debate. According to the current guideline, obtaining at least 16 lymph nodes is recommended, but in previous studies on advanced gastric cancer, some suggested mid-20 or 30 as a cut-off. This study aimed to find significant factors affecting successful lymphadenectomy for gastric cancer by applying a more stringent condition than the current guideline. Methods: A total of 1 948 patients who underwent laparoscopic and robotic gastrectomy for gastric cancer between January 2016 and February 2022 at Seoul St. Mary’s Hospital were recruited in this study. After exclusion, 393 patients with a pathologically advanced stage were included in the analysis, and their clinicopathological data, including the information about the indocyanine green (ICG)-guided lymphadenectomy, were retrospectively reviewed. Results: Among 393 patients, there were 288 patients in the conventional laparoscopy group (G1), 61 patients in the ICG-guided laparoscopy group (G2), and 44 patients in the ICG-guided robotic surgery group (G3). Patients in the G3 group had a significantly higher proportion of younger patients and a lower proportion with comorbidity. There was a similar trend in stage II and III ratio between the groups and the number of examined lymph nodes (ELNs) did not show a significant difference between groups (45.2±20.3 vs. 51.6±24.5 vs. 50.8±19.6, P=0.058). The ratio of 30 or fewer ELNs was the lowest in G3 (24% vs. 19.7% vs. 9.1%, P=0.050). The rate of exceeding 30 ELNs was increased in the case of higher node stage and more advanced cancer. In the multivariable analysis, the ICG-guided robotic surgery group was confirmed to be a significant factor for more than 30 ELNs (OR=3.151, 1.074~9.245, P=0.037). Conclusions: ICG-guided robotic gastrectomy could be useful in obtaining &gt;30 ELNs compared to conventional laparoscopic gastrectomy in selected cases.
Survival outcomes and functional results of VOLTAGE-A: Preoperative chemoradiotherapy (CRT) and consolidation nivolumab (nivo) in patients (pts) with both microsatellite stable (MSS) and microsatellite instability–high (MSI-H) locally advanced rectal cancer (LARC).
Authors: Yuichiro Tsukada, Hideaki Bando, Koji Inamori, Masashi Wakabayashi, Yosuke Togashi, Shohei Koyama, Daisuke Kotani, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Akinobu Taketomi, Mamoru Uemura, Takeshi Kato, Makoto Fukui, Motohiro Kojima, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

108 Background: In VOLTAGE-A, CRT (50.4 Gy with capecitabine of 1,650 mg/m 2 ) followed by five cycles of consolidation Nivo (240 mg q2 weeks [W]) and radical surgery showed 30% of pathological complete response (pCR) in pts with MSS and 60% in MSI-H T 3–4 N any M 0 LARC. Here, we report survival outcomes and functional results. Methods: All 39 MSS and 5 MSI-H pts were included in the VOLTAGE-A from Jan 2017 to Oct 2019. Survival outcomes, late adverse events, and patient-reported outcome measurements for urogenital and anal functions were analyzed. Urinary function was evaluated using the International Prostate Symptom Score (I-PSS) periodically at 1W, 1, 3, 6, and 12 months (M), postoperatively. Sexual function in sexually active male pts was evaluated using the International Index of Erectile Function (IIEF) score at 3, 6, and 12M, postoperatively. Anal function was evaluated using the Wexner score, low anterior resection syndrome (LARS) score, and fecal incontinence severity index (FISI) score at 1-year post-surgery. All functional scores were evaluated preoperatively. Results: With a median follow-up of 44.8M (range, 25.7-58.9M), the 3-year relapse-free survival (RFS) and 3-year overall survival (OS) rates were respectively 79.5% and 97.4% in MSS, and 100% each in MSI-H pts. Of the MSS pts, those with pCR, clinical CR (cCR) according to the MSKCC criteria, high PD-L1 expression (tumor proportion score [TPS] ≥1%), and CD8/eTreg ratios of ≥2.5 had a trend of better 3-year RFS and OS than those without. During the follow-up period, one patient developed CTCAE grade 3 immune-related colitis, which was diagnosed 20M after the last dose of Nivo. Postoperative functional results were acceptable in both populations; pre-surgical median I-PSS scores were 3, whereas postsurgical values were 5 (1W), 5.5 (1M), 5 (3M), 4 (6M), and 4 (12M); median IIEF score was 20 at pre-surgery and 6 (3M), 6 (6M), and 8 (12M) at post-surgery; median scores of Wexner, LARS, and FISI were 2, 23, and 7 at pre-surgery, and 9, 30, and 17 at 1-year post-surgery, respectively. Conclusions: Preoperative CRT followed by Nivo showed promising survival outcomes in both MSS and MSI-H LARC pts. The therapeutic effect of pCR, cCR, and certain biomarkers analyzed by pre-CRT samples could be used as prognostic predictors in MSS pts. Clinical trial information: NCT02948348 .[Table: see text]
Promoting multidisciplinary care for patients with unresectable hepatocellular carcinoma (HCC): Findings from a quality improvement initiative across two community cancer centers.
Authors: Ari David Baron, Bethany Delcuze, Francesca Guzzone, Jeffrey D. Carter, Cherilyn Heggen
Journal: Journal of Clinical Oncology (2023)

528 Background: Evolving treatment paradigms in HCC are increasing the need for multidisciplinary coordination and a focus on patient-centered care. Identifying real-world challenges HCC care teams face in implementing these critical practices is necessary to inform educational interventions and optimize patient outcomes. Methods: In March–April 2021, 22 health care professionals (HCPs) who treat HCC at 2 US community oncology clinics completed surveys assessing practice patterns, challenges, and confidence related to multidisciplinary and patient-centered care in HCC and participated in interdisciplinary audit and feedback sessions. Patient charts evaluated pre- and post-intervention assessed changes in clinical practice. Inclusion criteria included confirmed HCC diagnosis, age ≥ 18 years, and ≥ 2 visits in the one-year chart abstraction period. Results: Participants represented the interprofessional HCC care team: medical oncologists (38%), gastroenterologists (8%), hepatologists (4%), internal medicine (17%), advanced practice professionals (4%), and nurses (29%). Baseline and follow-up patient charts included 50% and 47% Stage II-III HCC patients and 50% and 53% Stage IV HCC patients, respectively. Top reported barriers to multidisciplinary tumor board use were ineffective interdepartmental coordination/collaboration (43%) and low volume of referrals (38%). HCPs aimed to resolve these gaps through improved collaboration between multidisciplinary teams (33%) and earlier referrals to a medical oncologist (29%). Providing patient-centered supportive care was identified by 33% of HCPs as the top challenge in HCC patient care. Of HCPs surveyed, 77% estimated that ≤ 25% of patients are evaluated for/referred to distress/behavioral health services. Chart audits after educational intervention and action plan implementation showed improvements in supportive care utilization (see table). A critical component of patient-centered care, shared decision-making (SDM) was reported by 24% of HCPs. HCPs reported patient resistance to SDM (33%) and low patient health literacy (29%) as top barriers to SDM. Chart documentation of HCP participation in SDM increased post intervention (see table). Conclusions: In current real-world practice, HCC care teams report challenges in interdisciplinary collaboration and referrals, providing supportive care, and involving patients in SDM. These identified gaps represent key opportunities for future interventions to improve HCC care. [Table: see text]
First-line anti-EGFR or anti-VEGF therapy, tumour sidedness, and survival: Results from the South Australian (SA) Metastatic Colorectal Cancer (mCRC) Registry.
Authors: Tharani Krishnan, Shahid Ullah, Cynthia Piantadosi, Christos Stelios Karapetis, Amanda Rose Townsend, Amitesh Roy, Barbara Geerinckx, Guy Maddern, David Roder, Rob Padbury, Timothy Price
Journal: Journal of Clinical Oncology (2023)

42 Background: The anti-EGFR monoclonal antibodies panitumumab (Pmab) and cetuximab (Cmab) and the anti-VEGF antibody bevacizumab (bev) have demonstrated clinical efficacy in mCRC in combination with first-line chemotherapy. Clinical and molecular characteristics, such as primary tumour sidedness, RAS, BRAF and MMR status are prognostic and predictive biomarkers for response to treatment. Our aim was to compare the survival and tumour characteristics of patients receiving first-line chemotherapy and antibody combinations using the SA mCRC Registry. Methods: This real-world registry has collected data from all patients diagnosed with mCRC in SA prospectively since 2006. We identified patients who had received first-line Pmab, Cmab or bev. Survival was analysed using the Kaplan-Meier method and log-rank test to compare outcomes based on primary tumour location. Results: Of the 5537 patients currently entered onto the registry, 1313 with RAS results available had received first-line anti-EGFR/VEGF antibodies and had colon tumour side recorded. The table summarises median overall survival (mOS) and patient characteristics. Survival was significantly shorter for those with right colon cancers (P &lt; 0.001). There were more high-grade (P &lt; 0.001), KRAS mutant (P = 0.004) and BRAF mutant (P = 0.036) tumours in those with right colon cancers, and a trend towards fewer curative liver resections (P = 0.059). There was no significant difference in mOS seen between Pmab, Cmab or bev for both left (P = 0.14) and right-sided (P = 0.88) primary tumours. Conclusions: There were more high-grade, BRAF and KRAS mutant patients with right colon tumours, and lower rates of liver resection, which may explain the significantly shorter mOS. The survival seen for Pmab and Cmab was almost identical for both right and left primary tumours. When comparing Pmab, Cmab and bev as first-line therapy, there was no significant difference in mOS for both left- and right-sided CRC. [Table: see text]
Incidence and clinical characteristics of patients with LAPC and mesenteric vein thrombosis and current treatment paradigm.
Authors: Amer H. Zureikat, Michael J. Pishvaian, Charles D. Lopez, Kenneth Meredith, Emmanuel E. Zervos, Hassan Hatoum, Ki Y. Chung, Alex Tsobanoudis, Daniel James Berg, Antonio Ucar, Reza Nazemzadeh, Susan Elaine Bates, Karyn A. Goodman, Thor Johnson, Nainesh Parikh, Brian Kouri, Christopher Laing, Brian A. Boone, Imtiaz Qureshi, Ramtin Agah
Journal: Journal of Clinical Oncology (2023)

714 Background: Mesenteric venous thrombosis (MVT), defined as complete occlusion of the Superior Mesenteric Vein (SMV) or Main Portal Vein (MPV) is often incidentally identified on CT or MRI in patients with Locally Advanced Pancreatic Cancer (LAPC). There is very limited data describing the incidence and treatment of MVT in large studies in this patient population. Herein, we seek to establish the incidence of MVT and the treatment response in patients with LAPC. Methods: We conducted an analysis on 180 subjects with interpretable baseline imaging for MVT enrolled in the randomized Phase III TIGeR-PaC clinical trial (NCT03257033). Subjects who completed 4 Cycles of induction treatment (3 cycles of IV gemcitabine/nab-paclitaxel and 1 cycle of IMRT or SBRT) prior to randomization were analyzed. Baseline and end of induction CT scans were read by a board-certified radiologist to determine presence of MVT. Severe MVT was defined as complete occlusion of MPV and/or SMV. For patients who completed induction the end of induction CT was used to assess down staging of MVT. We analyzed the mean age between patients with and without MVT using a Mann-Whitney test and performed a contingency table with Pearson Chi-Square statistics to analyze tumor location. Results: Out of a total of 180 patients, 91 patients presented with severe MVT at baseline (50%). There was no difference in age (67 vs. 69) or sex (44% male vs. 39% male) for patients with and without MVT. The location of the tumor in the head of the pancreas was more prevalent in both groups (62% vs 53%, respectively). Out of 112 patients who completed induction, 60 presented with MVT at baseline (53%). Seventeen of these patients (28%) demonstrated partial or complete resolution of MVT during induction; most resolved MVT after the first 2 cycles of chemotherapy (15/17). Only a minority of these patients were on anticoagulation therapy (10/60, 17%). Conclusions: Severe MVT is much more prevalent in patients with LAPC than previously reported. Anticoagulation is underutilized in this cohort; however, chemotherapy may have a beneficial effect in downstaging MVT beyond anticoagulation. Clinical trial information: NCT03257033 .
Discovery of novel interactions with LCK in cholangiocarcinoma using proximity-dependent biotinylation.
Authors: Jennifer L Tomlinson, Ryan D Watkins, Dong-Gi Mun, Caitlin Conboy, Akhilesh Pandey, Rory L Smoot
Journal: Journal of Clinical Oncology (2023)

575 Background: Cholangiocarcinoma (CCA) is a lethal hepatobiliary adenocarcinoma with increasing incidence and poor outcomes. Treatment success has been hindered by resistance, and new therapeutic strategies are necessary. The Src-family tyrosine kinase, LCK, activates Yes-associated protein (YAP), a known oncogene in CCA. While YAP has been historically difficult to target, we recently described LCK inhibition as a potential therapeutic option in CCA. We probed the LCK interactome employing biotinylation site identification technology (BioSITe) to discover molecular co-dependencies in the LCK-YAP axis. Methods: LCK-deficient HuCCT1, wild-type HuCCT1, and wild-type RBE cells were transfected with pEF-LCK-TurboID and used to reveal protein-protein interactions. Biotinylated peptides were enriched using anti-biotin antibodies followed by mass spectrometry analysis. Co-immunoprecipitation (Co-IP) was used to confirm interactions between LCK and identified interactors. Phosphoproteome profiling of human CCA tumors and patient derived xenografts was conducted to identify active kinase signatures in CCA. Tyrosine phosphorylated peptides were enriched using anti-phosphotyrosine antibody beads and analyzed by high-resolution mass spectrometery/liquid chromatography. Immunoblot analysis of HuCCT1 and LCK-deficient HuCCT1 cells was used to map the mechanistic interaction between LCK and epidermal growth factor receptor, EGFR. Inhibitors of EGFR and LCK, afatinib and NTRC 0652-0, respectively, were tested in vitro on human and murine CCA cell lines. Cell viability was determined with CellTiter-Glo; Calcusyn software was used to determine synergistic drug effects. Results: We discovered intracellular interactors of LCK in CCA using BioSITe. We identified both known and novel LCK interactors, including EGFR. Given that EGFR functions as a molecular driver of tumorigenesis and is increasingly recognized as a biomarker of resistance in a variety of tumors, we performed a phosphoproteomic evaluation of CCA tumors in which activated EGFR was identified by the presence of EGFR-Y1092, Y1197, and Y1172 phosphorylation. EGFR phosphorylation decreased under conditions of genetic LCK knock out and inhibition by NTRC 0652-0. Co-IP confirmed the interaction of EGFR with LCK. EGFR-Y1092 phosphorylation was downregulated with genetic knockout of LCK by immunoblot. Finally, EGFR inhibition was evaluated as a therapeutic strategy utilizing afatinib. Effects on cell viability were noted in both human and murine CCA cells. Afatinib and NTRC 0652-0 demonstrated a synergistic effect in vitro, with calculated combination indices of 0.007 – 0.790. Conclusions: A novel interaction between EGFR and LCK in CCA was identified using an unbiased proximity-dependent biotinylation technique. Dual blockade of LCK and EGFR is synergistic in CCA and may be a viable therapeutic approach for patients.
Is liquid biopsy useful in patients with GI malignancies and exclusive peritoneal disease?
Authors: Cristina Smolenschi, Marine Valery, Alice Boileve, Baptiste Cervantes, Anthony Tarabay, Valerie Boige, Imen Ben-Ammar, Bianca Cheaib, Maximiliano Gelli, Isabelle Sourouille, Leonor Benhaim, Alina Fuerea, Audrey Perret, Michel Ducreux, Antoine Hollebecque
Journal: Journal of Clinical Oncology (2023)

809 Background: Peritoneal carcinomatosis (PC) is a common manifestation in gastro-intestinal (GI) cancers.10-20 % of patients (pts) will present isolated, unresectable peritoneal disease with poor prognosis. In the past years, circulating tumor DNA (ctDNA) has emerged as a novel and less invasive biomarker for molecular diagnosis and disease monitoring. We aimed to evaluate the ability of PC to shed ctDNA into circulation in a cohort of pts with GI cancers and isolated PC treated in our institution. Methods: We reviewed retrospectively the results of liquid biopsies obtained at progression or at diagnosis. Genomic analysis was done using Foundation One liquid CDx panel. Data on demographics, tumor type, clinical outcomes and molecular alterations (MA) have been collected. Results: Out of 400 GI pts tested, 85 with exclusively PC were included in the analysis. The main characteristics were as follows: 45(53%) female, median age of 57 years (IQR: 24-79), majority have received systemic chemotherapy (all were progressive) (n=63, 74%) with median number of previous lines 1 (range: 0-3). Most common tumor types were as follows: gastric (n=24, 28%), colorectal (n=22, 26%) and primary peritoneal (n=20, 24%) cancers. The median index of peritoneal carcinomatosis was 23(IQR: 6-39). The tumor fraction was very low or undetectable in a proportion of 81% (n=69), median Tumor Mutational Burden was 1 mutation per megabase and was not correlated to tumor volume. Gene alterations were found in a proportion of 56% of pts (n=48) but most common alteration were TP 53 (n=22 pts, 26%) and KRAS mutation (n=14 pts, 16%). Targetable MA were identified only in 11 pts (13%) as follows: ATM, ARID1A, BRAFV600E, ERBB2, krasG12C. Three of them were included in a clinical trial. Germline mutations were found in 5 pts: ATM, CDH1, BRCA2, MSH6, BAP1. For colorectal pts known KRAS and BRAF V600E mutations were confirmed in plasma in a proportion of 32% (7 pts out of 22), for pancreatic cancer the KRAS in 17% (3 out of 18) and for gastric cancer, ERBB2 amplification in 5% (1 out of 22 pts). In pts with primary peritoneal disease: pseudomyxoma and mesothelioma, one patient harbored a known germline BAP 1 and kras G12C mutation without other targetable MA. The median survival in MA group was higher compared to non-MA. Conclusions: Isolated Pc and primary peritoneal cancers have distinct clinical and biological characteristics. The clinical utility of ctDNA seems to be limited in isolated PC or primary peritoneal cancers. However, it is not very clear if this to tumor location or to the ability of peritoneum to seed ctDNA.